Measurement of cholesterol levels has been known to be a predictor for various forms of coronary heart disease (CHD). The art has discovered that total cholesterol alone may not be adequate to identify subjects at risk for CHD and other conditions. For example, the predictive power of total cholesterol for risk of CHD diminishes in men with increasing age. In order to address this shortcoming, the measurement of various cholesterol fractions has been employed.
Measurement of various lipid parameters, whether alone or in combination, is known to correlate with various clinical outcomes, including, but not limited to, CHD, atherosclerosis, myocardial infarction and death. For example, plasma low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels have been shown to be important risk factors for CHD. In addition, total serum cholesterol is strongly correlated with the incidence of atherosclerosis and coronary heart disease. Furthermore, increased levels of LDL cholesterol have been associated with the greater risk of CHD, while a strong inverse relationship exists between HDL cholesterol and the risk of CHD. Elevation of plasma VLDL is seen in survivors of myocardial infarction, suggesting the possible involvement of this lipoprotein in the atheroschlerotic process.
As such, measurement of lipid parameters has become a valuable tool in the medical field. Recently, the distribution of cholesterol among all the lipoproteins (a lipoprotein cholesterol profile), in addition to total cholesterol, has been used to assess risk for coronary heart disease. Surprisingly, many patients remain at high residual risk even after “target” levels of lipids have been achieved.
To address this deficiency, the measurement of other parameters, such as apolipoprotein (apo) B (apo B) and apo A1, have been proposed for improving risk assessment. Apo B is the primary apolipoprotein of LDL, which is responsible for carrying cholesterol to tissues. While it is unclear exactly what functional role apo B plays in LDL, it is the primary apolipoprotein component and is absolutely required for LDL formation. Apo A1 is the major protein component of HDL in plasma and promotes cholesterol efflux from tissues to the liver for excretion. However, the predictive ability of these alternate parameters has not been adequately determined.
Therefore, the art is lacking methods to adequately predict the risk of CHD and/or clinical manifestations of CHD in a subject, particularly when the subject has reached target levels of one or more lipoproteins, such as, but not limited to, LDL or HDL or subclass of the foregoing. The present disclosure provides a solution to this need by providing methods to adequately predict the risk of CHD and/or clinical manifestations of CHD in a subject. In one embodiment, the method involves measuring the levels or concentration of apo A1, a subclass of HDL, specifically HDL3-C, or a combination of the foregoing. The methods of the present disclosure are particularly useful when the subject has reached target levels of one or more lipoproteins, such as, but not limited to, LDL or HDL or subclass of the foregoing